This invention relates to receptors for adhesion peptides, and more specifically to a novel receptor having affinity for fibronectin.
Multicellular organisms, such as man, have some 10.sup.14 cells which can be divided into a minimum of fifty different types, such as blood cells and nerve cells. During the course of growth and development, cells adhere to other cells, or to extracellular materials, in specific and orderly ways. Such cell adhesion mechanisms appear to be of importance in mediating patterns of cellular growth, migration and differentiation, whereby cells develop specialized characteristics so as to function as, for example, muscle cells or liver cells. Cell adhesion mechanisms are also implicated in dedifferentiation and invasion, notably where cells lose their specialized forms and become metastasizing cancer cells.
The mechanisms underlying the interactions of cells with one another and with extracellular matrices are not fully understood, but it is thought that they are mediated by cell surface receptors which specifically recognize and bind to a cognate ligand on the surface of cells or in the extracellular matrix.
The adhesion of cells to extracellular matrices and their migration on the matrices is mediated in many cases by the binding of a cell surface receptor to an Arg-Gly-Asp containing sequence in the matrix protein (as reviewed in Ruoslahti and Pierschbacher, Science 238:491(1987)). The Arg-Gly-Asp sequence is a cell attachment site at least in fibronectin, vitronectin, various collagens, laminin and tenascin. Despite the similarity of their cell attachment sites, these proteins can be recognized individually by the specific receptors.
Integrins are a family of adhesion receptors which bind to Arg-Gly-Asp binding sites of extracellular matrix membrane proteins via the Arg-Gly-Asp binding sites. They are heterodimeric molecules composed of one alpha (.alpha.) and one beta (.beta.) subunit. Several subunits of each kind are known, and various .alpha..beta. combinations make up receptors with different ligand specificities.
Eleven distinct alpha chains have thus far been described. Formerly, they have been divided into three main subfamilies based on the beta subunit with which they associate. The .beta..sub.1 subfamily includes receptors for fibronectin, various collagens, laminin and tenascin. The .beta..sub.2 subfamily consists of leukocyte specific receptors, while the .beta..sub.3 subfamily contains multispecific receptors commonly referred to as the platelet glycoprotein IIb-IIIa and the vitronectin receptor. Among the combinations known to exist, the .alpha..sub.v subunit associates with the .beta..sub.3 subunit to form a vitronectin receptor and with two recently described .beta. subunits called .beta..sub.x and .beta..sub.s. The .alpha..sub.v .beta..sub.x integrin is a vitronectin and fibronectin receptor while the ligand specificity of .alpha..sub.v .beta..sub.s is not known.
Because of the importance of integrins in mediating critical aspects of both normal and abnormal cell processes, there exists the need to identify and characterize different integrins. The present invention satisfies this need and provides related advantages as well.